The multiparametric physical method for diagnosis and test of curing cancer diseases based on Rayleigh light scattering is proposed. There was studied simultaneously dynamic and static parameters of blood plasma and serum proteins. A special device for this purpose is described and clinical results are presented.

The issues of early diagnosis and effective treatment of malignant neoplasms are of vital importance for the Urals region which in 1950-1960 became the site of several radiation incidents with the resultant overexposures of dozens of thousands of residents who have manifested increased risks of leukemia and solid cancer incidence. The present study has demonstrated the efficacy of the method of laser-correlation spectrometry (LCS) of blood plasma and serum for early diagnosis of malignant neoplasms and prediction of relapses of tumor following radical treatment. The LCS method is characterized by a sufficiently high diagnostic sensitivity in relation to malignant tumors. It has been established that LC spectra obtained for patients with malignant neoplasms differ significantly from those for patients with non-cancer pathology of the same sites. The LCS methodology has manifested a sufficiently high prognostic sensitivity (76.6%) in relation to complete regression after radical treatment and progression (78.0%) of the tumor process. A positive prognostic criterion of the course of a malignant neoplasm after radical treatment in patients without relapse and metastases is a statistically significant (p

Results of the research carried out at the Institute of Applied Physics US (IAP RAS) in collaboration with the Nizhny Novgorod Medical Academy are presented. The obtained data demonstrate capabilities of Optical Coherence Tomography (OCT), Polarization-Sensitive OCT (PS OCT), and Optical Coherence Microscopy (OCM) for biomedicine. Also we present our first results on Frequency-Domain Optical Diffusion Tomography (FD ODT) and Frequency-Domain Fluorescence Diffusion Tomography (FD FDT). OCT, CP OCT and OCT are high-resolution (3- 15 mcm) techniques used for visualization of near surface objects (at depths up to 2 mm). ODT and FDT have lower resolution (4-8 mm), but they allow investigation at depths up to 5-10 cm.

The double-wavelength differential molecular absorption technique with diode lasers is proposed for sensitive detection of functional status of breast tissues. The method is based on the measurement of the transmitted intensity differences of the two beams of diode lasers tuned to selected wavelengths within a broad absorption band of a human breast tissue within 700 - 800 nm spectral range. The strategy for the optimum selection of the diode laser wavelengths and initial adjustment of the detection scheme is developed. The method is demonstrated by the detection of the relative concentrations of two dyes, the optical properties of which are similar to those of a mixture of oxy- and deoxy- hemoglobin. The results of the first clinical tests of the proposed technique are briefly described.

A new diagnostic device KINOX created at P N Lebedev Physics Institute is described. With this device it is possible to trace the variations of oxygen permeability in erythrocyte membranes during the blood oxygenation. The molecular mechanism responsible for these variations was explained and experimentally tested at P N Lebedev Physics Institute. The diagnostic method is substantiated capable of estimating physiological reserves of organism basing on the results of blood oxygenation measurements performed with the KINOX. The possible reduction in physiological reserves of organism under the laser action on malignant tumor can be detected in this way.

The results of development and a setup of an industrial laser based on self-limited transitions of metal atoms are presented. The main technical characteristics of self-heating sealed-off active laser elements based on copper and gold vapor, as well as on the vapor mixture of copper and gold of the "KULON" series are presented. We also present the results of lifetime tests of copper vapor active elements and those obtained during standard tests together with the technical parameters of most powerful laser elements of this series. The developed industrial laser is manufactured in the form of a monoblock with overall dimensions 1250 x 330 x 190 mm and weight not exceeding 46 kg. Air cooling is forced. Such laser setups are designed for technological and medical applications.

In this work a new method for spectra fitting is presented. The method was named spectral coordinates fitting (SCF) because the central equation system is based on spectral coordinates. The method was validated on model spectra and spectra acquired during light intensity measurements during in-vivo Photodynamic Therapy (PDT) of dogs prostates.

The results of novel photosensitizer Photoditazine clinical trials have demonstrated high clinical potential of the drug in the PDT of 53 patients with malignant tumors. The drug has advantageous spectral, physico-chemical and energetic characteristics in comparison to currently used Russian and foreign photosensitizers.

The treatment of locally spread basal-cell skin cancer is very difficult and often complicated with local recurrence. Traditional techniques are sometimes insufficient for this pathology, especially for recurrent tumors. In the State Research Center for Laser Medicine photodynamic therapy had been used for treatment of 103 patients with locally spread basal-cell skin cancer, including 64 with recurrent tumors. Therapeutic effect has been achieved in all cases, including complete tumor resorption in 67% of patients. Presented paper contains analysis of immediate and long-term follow-up results.

Superficial transitional cell carcinoma represents 50 to 80% of newly diagnosed bladder cancer in various countries. Transurethral resection of the urinary bladder is the standard procedure for biopsy and treatment superficial bladder cancer. However recurrence tumors after transurethral resection alone is high enough (50-90%). Intravesical chemotherapy for prophylaxis after complete transurethral resection is reducing recurrence rate about 1 5%. Adjuvant intravesical Bacillus of Calmette and Guerin (BCG) is reducing recurrence rate about 30%, but frequency side effects of this therapy is very high. Purpose of this study is appreciate efficacy adjuvant PDT with photosensitizer Photogeme (Russia) of superficial bladder cancer for prophylaxis after complete transurethral resection. The follow up was from 3 to 63 months (27 months, on average). Sixty-five patients (75.6%) showed no recurrence. For the follow up period, the recurrence was revealed in 21 (24.4%) patient, in two of them it was progressing (one case of invasive growth and one case of remote metastases). Four cases of recurrence were revealed 4 months after the surgery. In other cases, the recurrence was diagnosed from 9 to 18 months.

Chlorine E6 derivative "Photoditazine" mediates photodynamic therapy (PDT) of tumours more effectively at higher doses. Both local and systemic effects were found in vivo. Synchronous PDT and selective distant laser hyperthermia (HT) are not advantageous. Excessive PDT and HT regimens leading to tumour necrosis increase the risk of tumour generalization.

The search for new pharmaceuticals has raised interest in locally-acting drugs which act over short distances within the cell, and for which different cell compartments have different sensitivities. Thus, photosensitizers used in anti-cancer therapy should be transported to the most sensitive subcellular compartments where their action is most pronounced. Earlier, we described the effects of bacterially expressed modular recombinant transporters for photosensitizers comprising a-melanocyte-stimulating hormone as an internalizable, cell-specific ligand, an optimized nuclear localization sequence, an Escherichia coli hemoglobin-like protein as a carrier, and an endosomolytic amphipathic polypeptide. These transporters delivered photosensitizers into the murine melanoma cells nuclei to result in cytotoxic effects 2 orders of magnitude greater than those of nonmodified photosensitizers. Here we describe new transporters possessing the same modules except for a ligand that is replaced with epidermal growth factor specific for other cancer cell types. The new transporter modules retained their functional activities within the chimera, this transporter delivered photosensitizers into the human carcinoma cells nuclei to result in photocytotoxic effects almost 3 orders of magnitude greater than those of nonmodified photosensitizers. The obtained results show that ligand modules of such transporters are interchangeable, meaning that they can be tailored for particular applications.

Di- and tri-sulfonated derivatives of metal-free phthalocyanine and Photosens have been compared in this study. In vitro phototoxicity was studied on HEp2, A549, and Colo26 cell cultures. It has been shown that phototoxicity of di- and tri- sulfonated derivatives of metal-free phthalocyanine exceeds phototoxicity of Photosens 5- and 8-times on HEp2 cell line, 8- and 6-times on A549 cell line, and 22-times on Colo26 cell line, respectively. In vivo photo-induced antitumor activity of metal-free phthalocyanine and Photosens was evaluated on mice with transplanted P388 lymphocytic leukemia. Dependence of photodynamic therapy efficiency on photosensitizer dose and time interval between preparation administration and irradiation was studied. It has been shown that Photosens is the most efficient in 5 mgikg of animal body weight dose and at 24-hour interval between injection and irradiation (tumor growth inhibition (TGI) - 82.2-95.6%). Metal-free phthalocyanine is the most efficient in 0.5 mg/kg dose which is 10- times lower than Photosens dose and when irradiated 4 hours later the injection (TGI - 78.6-100%). Metal-free di- and tri-sulfonated phthalocyanines are promising photosensitizers for photodynamic therapy. Taking into account its physical and chemical properties metal-free tri-sulfonated phthalocyanine named "Phthalosens" has been chosen for further thorough study.

Study is devoted to investigation of fluorescent and photodynamic properties of near-infrared photosensitizer bacteriochloriphyllide-serine. The peculiarities of its fluorescence excited by different lasers, dynamics and selectivity of accumulation were investigated. Photodynamic therapy of mice and investigation of tissue de-oxygenation during tumor irradiation were performed. It was shown that bacteriochloriphyllide-serine is an effective photosensitizer for PDT and fluorescent diagnostics of tumors.

Proc. SPIE 5973, In vivo evaluation of accumulation of sensitizers for oncological diagnostics and therapy using the method of diffuse reflectance spectroscopy, 59730H (7 December 2006); doi: 10.1117/12.640052

The article is devoted to in vivo investigations of absorption in biological tissue sensitized by preparations used for diagnostics and therapy of tumors. Efficiency of method of difhse reflectance spectroscopy for in vivo evaluation of accumulation of sensitizers is demonstrated.

This work is devoted to investigation of possibility to use the liposomal form of aluminium hydroxide tetra-3-phenylthiophthalocyanine as photosensitizer of near-infrared range. Aluminium hydroxide tetra-3-phenylthiophthalocyanine has shown high selectivity of accumulation in tumor comparing to normal tissue of mice as well as high photodynamic efficiency on mice bearing Erlich tumor (ELD) and lympholeucosis P-388. This compozition can be used to develop new effective photosensitizer for photodynamic therapy and fluorescent diagnostics.

The kinetic parameters of the cholesterol (in water) and tryptophane (in organic solvents) photooxidation sensitized by aminoacid derivatives of tetraphenylporphyrin immobilized on MF-4SK sulfocationic copolymer (analogue of N afion 117) were determined. It was shown that the activity of investigated systems depends on supramolecular structure of the polymer and on the type of porphyrin-polymer binding in organic solvents. In water, activity of investigated systems depends on supramolecular structure of the polymer only.

Transmembrane potentials appear to be cell state sensitive characteristics and can give information about cell damage initial stage. Photodynamic action of the photosensitizer chlorin e6 on plasmatic and mitochondrial membrane potentials of the rat thymus lymphocytes was studied using voltage-sensitive dye rhodamine 6G. It has been revealed that mitochondrial membrane potential is more sensitive characteristic of membrane disfunction than plasmatic one at the cell photodamage.

A new method for spectral data formalization was developed. Spectral coordinates allows extracting specific properties of spectral components in order to convert physical experimental data into diagnostic data. Also visualization method is presented which allows placing spectral coordinates as a point onto orthogonal coordinates in order to perform statistical data accumulation, data clustering, and making following diagnostic assumptions. As experimental test data spectra collected in-vivo in patients were used.

The obtained clinical findings demonstrate excellent results after surgical MSC treatment with the application of modem laser surgical technologies. All the operated patients were under oncologist's control during 1.5-2.5 years. In 6 cases we observed topical recurrences which needed a repeated intervention. Thus, our experience of applying LPh for surgical treatment of basal-cell carcinomas of the head and neck dem- onstrate that in the analysed cases it is more reasonable to use two models of laser devices different in their physical parameters. These devices are used at different surgical stages so as to provide a precise effect in laser tumour vaporization within the borders of the healthy tissue, to make better vascular coagulation and laser smoothing of wound surface. Immediate, direct and long-term results of modern surgical lasers' application for treating skin BSC almost in all cases give good and excellent cosmetic effect after such intenventions.

In report summarized more then 10 experience of authors in Novosibirsk Traumatology and orthopedics research institute Neurosurgery clinic on usage of laser technologies in treatment of central nervous system tumors. On the basis of ND-YAG laser application original technologies have been developed and used in surgical treatment of patients with various neurosurgical pathology and protected by 8 Patents of the Russian Federation. 427 patients were operated on with the use of YAG:Nd3+ laser. Out of them 152 patients had extracerebral tumors of various volume and localization, 135 patients - spinal cord tumors, 74 patients - a pathology of cerebrospinal transition (Amold-Chiari syndrome of 1-2 types), and 66 patients - intramedullary tumors of deep localization. Results showed good results of laser technologies usage for central nervous system tumors removal.

The results of the 5-year epidemiological and pathological investigations of cutaneous basal-cell carcinomas from inhabitants of the St. Petersburg area, removed with COz and Yachroma-Med copper vapor laser are presented. By our analysis of the intensity of exogenous impacts upon the tumor morbidity rate, we have concluded the industrial hazardous factors to be a dominant in this influence. The correlation between histological type and wide range of clinical behavior was proved.

An analytical procedure to study linear thermal processes in multilayered biological tissues irradiated by a laser beam is proposed. The procedure is based on the simplified representation of the heat source function after the irradiation. The Green function of both temporal and radial coordinates of the thermal problem is analytically derived in the paper. It enables one to easy simulate spatial and temporal temperature distributions in tissue by a simple convolution. Pulsed or continuous-wave laser beams with any radial structures can be treated. The validity of the approximations assumed to get the Green function is verified by comparing the simulations with published data on both light and thermal fields in tissues. Rather a good agreement is shown. Specific attention is paid to the most critical approximation, namely to the separation of radial and depth coordinates in the thermal source function. The applicability of such an approach is discussed and quantitatively checked by evaluating the temporal dynamics of radial light and heat spot spreading. The procedure is used to study thermal processes in irradiated skin layers under wide variations of optical parameters of the problem. Sample results on the heating effects of a sensitizer used for photodynamic therapy are illustrated.

This paper considers the problems of application of high-power semiconductor lasers for designing multifunctional laser therapeutic devices (MLTD) and the prospects of their use in oncology and other areas of medicine. It is shown that the MLTD allows the realization of the method of combined photodynamic therapy (PDT) and laser-induced thermotherapy (LITT) in treatment of oncology diseases of different localizations. The technology for treatment of cancer based on the method of combined PDT and LITT and the MLTD device conforms to the advanced world tends in treatment of oncology diseases with the use of laser radiation. The problems of interaction of laser radiation with a biological tissue in oncology and therapy of various pathologies are briefly considered, and the list of the main functional parameters of the MLTD is formulated. The problems of designing the hardware and algorithrmc software of the MLTD, the technical and user characteristics are considered, including the features of automatic digital c ontrol of laser power depending on the level of temperature of a biological tissue. The areas of medicine where the MLTD can be used with the most efficiency are shown.

New method based on techniques of self-induced autodyne effect for diagnostics and control of laser-tissue evaporation by radiation of high-frequency pumped waveguide CO2 laser is developed. This method is used for creation of feed-back for smart CO2 laser surgical system of "Lancet" series. The results of medical testing of the smart laser surgical system are presented.

The sizeable damage of tumor (Pliss lymphosarcoma) were detected on intact rats (without the photosensitizer injection) after laser excitation (λ=627.8 nm or λ=671 nm). The model is suggested to calculate the absolute and relative sizes of the tumor node necrosis and the area of the histotopographic section. The photon distribution between photosensitizer and hemoglobin molecules is calculated for the typical PDT conditions. We suppose that some non-photodynamic reactions activated by light are responsible for the observed photodestructive effect on intact tumors. The contribution of these reactions to the tumor damage in PDT treatments is considerable and it cannot be neglected.

Under high-intensity laser pulses the morphology and size of the crater induced in biotissue depends both on biotissue properties and on irradiation conditions. The objective of this study is to correlate the wound morphology and patterns of microdestruction with the mechanisms of interaction. Along with the regime of superficial layerwise evaporation of tissue induced by C02 medical, or selective photocoagulation induced by copper vapor lasers, the present work describes the regime of bulk selective damage of coloration centers that are irregularly distributed in the deep of the tissue. Photo induced disruption is the mechanism responsible for it.

The light-oxygen effect (LOE) represents damage (and at low optical doses, activation) of cells by photogeneration of molecular singlet oxygen from Oz dissolved in cells, in accordance with the reaction: 302 + hv--> lO2--> biological effect. The phases of evolution of the LOE are similar to the phases, of the photodynamic effect (PDE), the mechanism of which is the basis of the familiar method of photodynamic tumour therapy. An evidence of the occurrence of the LOE are in the form of detailed spectra of the biological action of optical radiation on cells. Identification of the primary photoacceptor (02) in cell biostimulation and photodestruction provides a scientific basis for the development of light-oxygen tumour therapy methods. Results are given of the first experimental applications of the LOE in tumour therapy.

Temperature-dependent transient processes initiated by a direct photogeneration of singlet oxygen in suspensions of human erythrocytes and solutions of serum albumin are studied. The processes appear as anomalous jumps in the temperature dependences of the deformability coefficient of erythrocytes and the refractive index of the extracellular medium and protein solution. In the temperature regions of anomalous jumps, cells and proteins transfer to a metastable state of a lower activity, but they can be isothermally photoreactivated. Simultaneously, a reversible rearrangement of the aqueous phase occurs near the cell and protein surfaces, accompanied by the formation of an extended corona (hydrogel). The transient processes are interpreted as phase transitions in the membrane of erythrocytes and conformation transitions in proteins. The interaction between erythrocytes and albumin via hydrogel is discovered (hydro-conformational interaction).

Infrared laser radiation of low intensity in exposition dose of 25-35 mJicm2 does not cause progress the tumor process. Moreover, disturbing the blood flow in the tumor due to changing synthesis of norepinephrine and histamine this radiation contributes to the damage of the tumor tissue accompanied by the beginning of adaptation reaction in the organism.

Beside the classical photodynamic therapy (PDT) procedure, another possible mode of PDT treatment exists. In the latter case the light does not have to be delivered directly to tumor as soon as it is not always technically possible. In some cases systemic cytotoxic effects of photomodified blood can cause tumor damage. Possibly this happens due to apoptosis induction. These observations broaden possible PDT applications significantly.

This short review reflects the latest achievements of technical science for medicine in the field of creating phototherapeutic technologies for oncology. The article discuss the problem of further developing and applying matrix phototherapeutic apparatus. The comparison and the features of alternative sources based on light emitted diodes structures are considered. The application of photomatrix system for photodynamic therapy and for postmastectomy oedema treatment are presented.

Physical methods are widely spread in diagnostics and therapy of different pathologies, especially in oncology. The application of lasers occurred to be the perspective approach for combined methods application in medicine. Our work is devoted to investigation of thermal effect of focused laser beam in the model of Garding-Passi melanoma and also to the study of free radicals activity after the radiation with non-focused laser beam. The histologic alterations correlated with theoretical calculations of temperature distribution in irradiated tissue for energies 30-60 J attracted our interest. The values of maximal temperatures in depths of tissue for energies 30-60 J were carried out. In the model of permanent magnetic field (PMF) effect for mice ascites sarcoma 37 we have showed the linear dependence of tumor growth inhibition from the period of PMF treatment. Simultaneously we investigated PMF influence for free radical's (FR) concentrations in mice organs and tissues and potentially appearing questions of PMF effect for biopotential in connection with FR formation. We have also studied the alterations of K, Na and Ca ions concentrations in ascetic fluids after animal's PMF treatment. We revealed some reasons of biopotential generation and concluded that biopotential is not the result of specific ions gradient only but its generation can be followed by free radicals states appearance and occurrence of semi-conductivity in biostructures.

Nowadays an attention is paid to pathbreaking approaches to the therapy of different pathologies with EPR, NMR and NGR dialysis and mechanisms of physical factors influence in prophylactics and therapy of a number of diseases. Any pathology is evidently begins its development in atomic-molecular levels earlier then any morphologic alterations in tissues can be detected. We have studied the alterations of FR content in liver, spleen and brain in hypoxia and hyperoxia conditions. Under hypoxia and hyperoxia the FR concentrations are equal in all organs and tissues. However this ratio is different for some forms of leucosis. For different leucosis types gas mixtures the most adequate for the current pathology should be developed. Then we represent the method of biologic objects treatment with the energy of super-high frequency field (SIT) and the instrument for its performance. The study of magnetic heterogeneity of biologic systems proposes the new approach and a set of methods for medical and scientific purpose. Application of combined with chemotherapy extraction of anionic and cationic radicals from bloodstream using EPRD, NMRD and NGRD influence and also the single ions separate extraction using NGRD are able to detect and perhaps to cure their appearance in a period before neoformation. These studies should be carried out experimentally and clinically.

The combination of fluorescence spectroscopy and optical trapping under an integrated laser scanning microscopy platform has presented to be a powerful tool in manipulating and positioning the cells as well as standardizing the conditions of measurements. This platform was applied to investigate the autofluorescence of PC12 cells. Under 2-p excitation, the PC12 cells exhibit fluorescence in the range of 500-530 nm. It was shown that intensity of 2-p autofluorescence from PC12 cells is very sensitive to the cells' condition. Therefore autofluorescence from the cells may be a convenient and noninvasive method for monitoring the cell's or another biological object's condition, metabolism, and/or vitality under various physical and chemical influences.

In the given research the new method of fluorescent diagnostics (FD) and photodynamic therapy (PDT) control of acne disease is submitted. Method is based on simultaneous diagnostics in natural and fluorescent light. PDT was based on using 5-ALA (5- aminolevulinic acid) preparation and 600-730 nanometers radiation. If the examined site of a skin possessed a high endogenous porphyrin fluorescence level, PDT was carried out without 5-ALA. For FD and treatment control a dot spectroscopy and the fluorescent imaging of the affected skin were used.

Psoriasis is a chronic, genetically-determined disease, characterized by an immuno-mediated pathogenesis. Treatment of psoriasis is often complicated and remains a challenge. Along with the many new immunomodulatory approaches, various laser systems have been employed for chronic plaque psoriasis treatment. Recently, it has been demonstrated that the light produced by xenon-chloride excimers (generated by sophisticated devices with peak emission of 308 nm) is effective in the treatment of several psoriasis forms. We treated patients, ranging in age from 35 to 55 years, affected by plaque-type psoriasis vulgaris with monochromatic excimer light (MEL). We used MEL in a complex with basic treatment. Therapy was administered three times a week. At the end of the 3th week of treatment all patients showed an improvement, as evidenced by flattening of plaques, decreased scaling and erythema, and decreased vesicle and pustule formation. Unwanted side effects such as pain, blistering was not observed. Minimal erythema and a hyperpigmentation were noted in some patients. It was concluded that the MEL therapy may be a valuable option for treatment of plaque-type psoriasis vulgaris in shorter time compare with traditional NB UVB, with exposure to lower cumulative doses

During the last several years researches have been carried out in order to study the possibility of autofluorescence diagnostics application in dentistry for caries and different periodontium tissues diseases diagnostics. We carried out the research of periodontium tissues autofluorescence images and spectra to develop the method of autofluorescence diagnostics of premorbid conditions of inflammatory periodontium tissues diseases.

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Journal of Applied Remote SensingJournal of Astronomical Telescopes Instruments and SystemsJournal of Biomedical OpticsJournal of Electronic ImagingJournal of Medical ImagingJournal of Micro/Nanolithography, MEMS, and MOEMSJournal of NanophotonicsJournal of Photonics for EnergyNeurophotonicsOptical EngineeringSPIE Reviews